Cerebral function parameters in people with HIV switching integrase inhibitors: a randomized controlled trial.

Different antiretroviral therapies (ARTs) may have differing effects on central nervous system (CNS) function. We assessed CNS pharmacodynamic effects of switching integrase inhibitors in people-with-HIV (PWH). PWH on tenofovir-DF/emtricitabine plus raltegravir 400 mg twice daily with suppressed plasma HIV RNA and without overt neuropsychiatric symptoms were randomly allocated on a 1:2 basis to remain on raltegravir or switch to dolutegravir 50 mg once daily for 120 days. Pharmacodynamic parameters assessed included cognitive function (-score of 7 domains), patient-reported outcome measures (PROMs; PHQ-9 and Beck's depression questionnaires), cerebral metabolite ratios measured by proton magnetic resonance spectroscopy (H-MRS) and plasma and cerebrospinal fluid (CSF) HIV RNA. Pharmacokinetic parameters were also assessed in plasma and CSF. Changes and factors associated with changes in pharmacodynamics parameters were assessed.In 20 subjects (19 male, 14 white ethnicity, median age 43 years (IQR: 11.5) and CD4 + count 717 (SD: 298) cells/µL), over 120 days there were no statistically significant changes in cognitive function [mean -score difference (95%CI) -0.004 (-0.38/0.37);  = 0.98], PROMs [PHQ-9 median score change: 0 in control arm, -0.5 switch arm ( = 0.57); Beck's depression questionnaire: -1.5 control arm, -1.0 switch arm ( = 0.38)], nor cerebral metabolite ratios between study arms. CSF HIV RNA was <5 copies/mL at baseline and day 120 in all subjects. Geometric mean pre-dose CSF dolutegravir concentration was 7.6 ng/mL (95% CI: 5.2-11.1).Switching integrase inhibitor in virologically suppressed PWH without overt neuropsychiatric symptoms resulted in no significant changes in an extensive panel of CNS pharmacodynamics parameters.